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Multicentric Assessment of the Hong Kong Liver Cancer Staging System in Chinese Patients Following Transarterial Chemoembolization

  • Clinical Investigation
  • Interventional Oncology
  • Published:
CardioVascular and Interventional Radiology Aims and scope Submit manuscript

Abstract

Purpose

We aimed to validate the performance of the hepatitis B-based Hong Kong Liver Cancer (HKLC) staging system compared with the Barcelona Clinic Liver Cancer (BCLC) staging system in Chinese hepatocellular carcinoma (HCC) patients treated with conventional transarterial chemoembolization (TACE) as the initial treatment.

Materials and Methods

The study was approved by the Institutional Review Boards at all participating centers. This retrospective study included 715 patients with HCC who underwent TACE as the initial treatment between January 2008 and December 2016 at three Chinese institutions. All of the patients calculated HCC stage using 5-substage HKLC (HKLC-5), 9-substage HKLC (HKLC-9), and the BCLC system. Based on overall survival (OS), these three staging systems’ performance on treatment outcome prediction were compared using C statistic, Akaike information criterion (AIC), area under the receiver operating characteristic curve (AUC), linear trend Chi-square, likelihood ratio Chi-square, and calibration plots, respectively.

Results

The median OS was 10.1 months. Compared with the BCLC system, the HKLC system, especially HKLC-9, showed better performance on survival prediction (HKLC-9: C = 0.689, AIC = 6646.162; HKLC-5: C = 0.683, AIC = 6662.663; BCLC: C = 0.680, AIC = 6654.146), homogeneity (likelihood ratio Chi-square: HKLC-9 = 232.38, HKLC-5 = 215.87, and BCLC = 224.39, P < 0.001), and calibration (R2: HKLC-9 = 0.923, HKLC-5 = 0.916, and BCLC = 0.914). HKLC-9 outperformed on AUC at 6-, 12-, and 24-month survival prediction than HKLC-5 and BCLC. BCLC showed better performance on monotonicity (linear trend Chi-square: HKLC-9 = 121.641, HKLC-5 = 117.389, and BCLC = 125.752; P < 0.001).

Conclusions

Combining survival prediction, discrimination, and calibration, the HKLC, especially HKLC-9 system, performed better for Chinese patients treated with TACE than the BCLC system.

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References

  1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108. https://doi.org/10.3322/caac.21262.

    Article  PubMed  Google Scholar 

  2. Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115–32. https://doi.org/10.3322/caac.21338.

    Article  PubMed  Google Scholar 

  3. Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018. https://doi.org/10.1016/S0140-6736(18)30010-2.

    Article  PubMed  Google Scholar 

  4. Yang JD, Kim WR, Park KW, Chaiteerakij R, Kim B, Sanderson SO, et al. Model to estimate survival in ambulatory patients with hepatocellular carcinoma. Hepatology. 2012;56(2):614–21. https://doi.org/10.1002/hep.25680.

    Article  PubMed  Google Scholar 

  5. Vauthey JN, Klimstra D, Blumgart LH. A simplified staging system for hepatocellular carcinomas. Gastroenterology. 1995;108(2):617–8.

    Article  CAS  PubMed  Google Scholar 

  6. Llovet JM, Bru C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis. 1999;19(3):329–38. https://doi.org/10.1055/s-2007-1007122.

    Article  CAS  PubMed  Google Scholar 

  7. Leung TW, Tang AM, Zee B, Lau WY, Lai PB, Leung KL, et al. Construction of the Chinese University Prognostic Index for hepatocellular carcinoma and comparison with the TNM staging system, the Okuda staging system, and the Cancer of the Liver Italian Program staging system: a study based on 926 patients. Cancer. 2002;94(6):1760–9.

    Article  PubMed  Google Scholar 

  8. Kudo M, Chung H, Osaki Y. Prognostic staging system for hepatocellular carcinoma (CLIP score): its value and limitations, and a proposal for a new staging system, the Japan Integrated Staging Score (JIS score). J Gastroenterol. 2003;38(3):207–15. https://doi.org/10.1007/s005350300038.

    Article  PubMed  Google Scholar 

  9. European Association for the study of the L, European Organisation for R, Treatment of C. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56(4):908–43. https://doi.org/10.1016/j.jhep.2011.12.001.

    Article  Google Scholar 

  10. Bruix J, Sherman M, American Association for the study of liver D. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53(3):1020–2. https://doi.org/10.1002/hep.24199.

    Article  PubMed  Google Scholar 

  11. Zhong JH, Ke Y, Gong WF, Xiang BD, Ma L, Ye XP, et al. Hepatic resection associated with good survival for selected patients with intermediate and advanced-stage hepatocellular carcinoma. Ann Surg. 2014;260(2):329–40. https://doi.org/10.1097/SLA.0000000000000236.

    Article  PubMed  Google Scholar 

  12. Daniele B, Annunziata M, Barletta E, Tinessa V, Di Maio M. Cancer of the Liver Italian Program (CLIP) score for staging hepatocellular carcinoma. Hepatol Res Off J Jpn Soc Hepatol. 2007;37(Suppl 2):S206–9. https://doi.org/10.1111/j.1872-034X.2007.00186.x.

    Article  Google Scholar 

  13. Bolondi L, Burroughs A, Dufour JF, Galle PR, Mazzaferro V, Piscaglia F, et al. Heterogeneity of patients with intermediate (BCLC B) hepatocellular carcinoma: proposal for a subclassification to facilitate treatment decisions. Semin Liver Dis. 2012;32(4):348–59. https://doi.org/10.1055/s-0032-1329906.

    Article  CAS  PubMed  Google Scholar 

  14. Yau T, Tang VY, Yao TJ, Fan ST, Lo CM, Poon RT. Development of Hong Kong Liver Cancer staging system with treatment stratification for patients with hepatocellular carcinoma. Gastroenterology. 2014;146(7):1691–700. https://doi.org/10.1053/j.gastro.2014.02.032.

    Article  PubMed  Google Scholar 

  15. Park JW, Chen M, Colombo M, Roberts LR, Schwartz M, Chen PJ, et al. Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE Study. Liver Int Off J Int Assoc Study Liver. 2015;35(9):2155–66. https://doi.org/10.1111/liv.12818.

    Article  Google Scholar 

  16. Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol. 2001;35(3):421–30.

    Article  CAS  PubMed  Google Scholar 

  17. Zhong BY, Ni CF, Chen L, Zhu HD, Teng GJ. Early sorafenib-related biomarkers for combination treatment with transarterial chemoembolization and sorafenib in patients with hepatocellular carcinoma. Radiology. 2017;284(2):583–92. https://doi.org/10.1148/radiol.2017161975.

    Article  PubMed  Google Scholar 

  18. Marelli L, Stigliano R, Triantos C, Senzolo M, Cholongitas E, Davies N, et al. Transarterial therapy for hepatocellular carcinoma: which technique is more effective? A systematic review of cohort and randomized studies. Cardiovasc Interv Radiol. 2007;30(1):6–25. https://doi.org/10.1007/s00270-006-0062-3.

    Article  Google Scholar 

  19. Terzi E, Golfieri R, Piscaglia F, Galassi M, Dazzi A, Leoni S, et al. Response rate and clinical outcome of HCC after first and repeated cTACE performed “on demand”. J Hepatol. 2012;57(6):1258–67. https://doi.org/10.1016/j.jhep.2012.07.025.

    Article  CAS  PubMed  Google Scholar 

  20. Ueno S, Tanabe G, Sako K, Hiwaki T, Hokotate H, Fukukura Y, et al. Discrimination value of the new western prognostic system (CLIP score) for hepatocellular carcinoma in 662 Japanese patients. Cancer of the Liver Italian Program. Hepatology. 2001;34(3):529–34. https://doi.org/10.1053/jhep.2001.27219.

    Article  CAS  PubMed  Google Scholar 

  21. Memon K, Kulik LM, Lewandowski RJ, Wang E, Wang J, Ryu RK, et al. Comparative study of staging systems for hepatocellular carcinoma in 428 patients treated with radioembolization. J Vasc Interv Radiol JVIR. 2014;25(7):1056–66. https://doi.org/10.1016/j.jvir.2014.01.010.

    Article  PubMed  Google Scholar 

  22. Harrell FE Jr., Lee KL, Mark DB. Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med. 1996;15(4):361–87. https://doi.org/10.1002/(SICI)1097-0258(19960229)15:4<361::AID-SIM168>3.0.CO;2-4.

    Article  PubMed  Google Scholar 

  23. Steyerberg EW, Vickers AJ, Cook NR, Gerds T, Gonen M, Obuchowski N, et al. Assessing the performance of prediction models: a framework for traditional and novel measures. Epidemiology. 2010;21(1):128–38. https://doi.org/10.1097/EDE.0b013e3181c30fb2.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Adhoute X, Penaranda G, Bronowicki JP, Raoul JL. Usefulness of the HKLC vs. the BCLC staging system in a European HCC cohort. J Hepatol. 2015;62(2):492–3. https://doi.org/10.1016/j.jhep.2014.08.035.

    Article  PubMed  Google Scholar 

  25. Sohn JH, Duran R, Zhao Y, Fleckenstein F, Chapiro J, Sahu S, et al. Validation of the Hong Kong Liver Cancer staging system in determining prognosis of the North American patients following intra-arterial therapy. Clinical Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2017;15(5):746–55. https://doi.org/10.1016/j.cgh.2016.10.036.

    Article  Google Scholar 

  26. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. New Engl J Med. 2008;359(4):378–90. https://doi.org/10.1056/NEJMoa0708857.

    Article  CAS  PubMed  Google Scholar 

  27. Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10(1):25–34. https://doi.org/10.1016/S1470-2045(08)70285-7.

    Article  CAS  PubMed  Google Scholar 

  28. Yoo DJ, Kim KM, Jin YJ, Shim JH, Ko GY, Yoon HK, et al. Clinical outcome of 251 patients with extrahepatic metastasis at initial diagnosis of hepatocellular carcinoma: Does transarterial chemoembolization improve survival in these patients? J Gastroenterol Hepatol. 2011;26(1):145–54. https://doi.org/10.1111/j.1440-1746.2010.06341.x.

    Article  PubMed  Google Scholar 

  29. Pinter M, Hucke F, Graziadei I, Vogel W, Maieron A, Konigsberg R, et al. Advanced-stage hepatocellular carcinoma: transarterial chemoembolization versus sorafenib. Radiology. 2012;263(2):590–9. https://doi.org/10.1148/radiol.12111550.

    Article  PubMed  Google Scholar 

  30. Luo J, Guo RP, Lai EC, Zhang YJ, Lau WY, Chen MS, et al. Transarterial chemoembolization for unresectable hepatocellular carcinoma with portal vein tumor thrombosis: a prospective comparative study. Ann Surg Oncol. 2011;18(2):413–20. https://doi.org/10.1245/s10434-010-1321-8.

    Article  PubMed  Google Scholar 

  31. Lee YS, Seo YS, Kim JH, Lee J, Kim HR, Yoo YJ, et al. Can more aggressive treatment improve prognosis in patients with hepatocellular carcinoma? A direct comparison of the Hong Kong Liver Cancer and Barcelona Clinic Liver Cancer algorithms. Gut Liver. 2017. https://doi.org/10.5009/gnl17040.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Wallace MC, Huang Y, Preen DB, Garas G, Adams LA, MacQuillan G, et al. HKLC triages more hepatocellular carcinoma patients to curative therapies compared to bclc and is associated with better survival. Dig Dis Sci. 2017;62(8):2182–92. https://doi.org/10.1007/s10620-017-4622-y.

    Article  PubMed  Google Scholar 

  33. Chapiro J, Geschwind JF. Hepatocellular carcinoma: have we finally found the ultimate staging system for HCC? Nature Rev Gastroenterol Hepatol. 2014;11(6):334–6. https://doi.org/10.1038/nrgastro.2014.67.

    Article  Google Scholar 

  34. Min YW, Kim J, Kim S, Sung YK, Lee JH, Gwak GY, et al. Risk factors and a predictive model for acute hepatic failure after transcatheter arterial chemoembolization in patients with hepatocellular carcinoma. Liver Int Off J Int Assoc Study Liver. 2013;33(2):197–202. https://doi.org/10.1111/liv.12023.

    Article  CAS  Google Scholar 

  35. Choi TW, Kim HC, Lee JH, Yu SJ, Kang B, Hur S, et al. The safety and clinical outcomes of chemoembolization in Child–Pugh class C patients with hepatocellular carcinomas. Korean J Radiol. 2015;16(6):1283–93. https://doi.org/10.3348/kjr.2015.16.6.1283.

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

This study was funded by the National Basic Research Program of China (973 Program #2013CB733800, 2013733803), the National Scientific and Technical Achievement Translation Foundation ([2012]258), the National Natural Science Foundation of China (81441054, 81671796, 81501522), the Jiangsu Provincial Special Program of Medical Science (BL2013029), the Fundamental Research Funds for the Central Universities, and the Scientific Research Innovation Program for College and University Graduates of Jiangsu Province (KYZZ16_0133). Funding sources had no involvement in the financial support for the conduct of the research and preparation of the article.

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Author notes

  1. Bin-Yan Zhong, Cai-Fang Ni, and Guo-Wen Yin have contributed equally to this work.

Authors and Affiliations

  1. Department of Radiology, Zhongda Hospital, Medical School, Southeast University, 87 DingjiaqiaoRoad, Nanjing, 210009, China

    Bin-Yan Zhong, Li Chen, Hai-Dong Zhu, Jin-He Guo, Shi-Cheng He, Gang Deng, Qi Zhang & Gao-Jun Teng

  2. Department of Interventional Radiology, First Affiliated Hospital of Soochow University, Suzhou, China

    Cai-Fang Ni & Pei-Cheng Li

  3. Department of Interventional Radiology, Cancer Hospital of Jiangsu Province, Cancer Institution of Jiangsu Province, Nanjing, China

    Guo-Wen Yin & Hui Yu

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  1. Bin-Yan Zhong
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Correspondence to Gao-Jun Teng.

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Ethical Approval

Our study was approved by the Institutional Review Boards (IRBs) at three participating centers. The requirement to obtain informed consent was waived due to the retrospective nature.

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The requirement to obtain informed consent was waived due to the retrospective nature of this study.

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Zhong, BY., Ni, CF., Yin, GW. et al. Multicentric Assessment of the Hong Kong Liver Cancer Staging System in Chinese Patients Following Transarterial Chemoembolization. Cardiovasc Intervent Radiol 41, 1867–1876 (2018). https://doi.org/10.1007/s00270-018-2023-z

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